Question
What are prions. Name human prion diseases. Discuss in detail any one of them. (1+3+4)
Answer
Prions: infectious, misfolded proteinaceous particles devoid of any nucleic acid (unlike conventional infectious agents), capable of causing disease by inducing the conformational conversion of the normal host cellular prion protein (PrP^C, predominantly alpha-helical) into an abnormal, disease-associated isoform (PrP^Sc, predominantly beta-sheet-rich), which is protease-resistant, aggregation-prone, and accumulates in neural tissue, causing progressive neurodegeneration. Prion diseases are collectively termed transmissible spongiform encephalopathies (TSEs), characterized pathologically by neuronal loss, spongiform (vacuolar) change, and astrogliosis, without any accompanying inflammatory response.
Human prion diseases:
- Creutzfeldt-Jakob Disease (CJD) — sporadic, familial, iatrogenic, and variant (vCJD) forms.
- Kuru.
- Gerstmann-Sträussler-Scheinker (GSS) syndrome.
- Fatal Familial Insomnia (FFI).
Detailed discussion — Creutzfeldt-Jakob Disease (CJD)
Forms: Sporadic CJD (the most common form, ~85% of cases, arising from a spontaneous conformational conversion event, cause unknown); Familial CJD (associated with inherited mutations in the PRNP gene); Iatrogenic CJD (transmitted via contaminated neurosurgical instruments, corneal transplant, dura mater grafts, or cadaveric growth hormone — reflecting the organism’s remarkable resistance to standard sterilization methods); and Variant CJD (vCJD) — linked to consumption of cattle products contaminated with the agent of Bovine Spongiform Encephalopathy (“mad cow disease”).
Clinical features: rapidly progressive dementia, myoclonus, ataxia, visual disturbance, and behavioural changes, progressing to akinetic mutism and death, typically within months of symptom onset (a notably rapid course compared to other dementias).
Laboratory diagnosis:
- EEG — characteristic periodic sharp-wave complexes (particularly in sporadic CJD).
- MRI brain — cortical ribboning and basal ganglia hyperintensity on diffusion-weighted imaging.
- CSF 14-3-3 protein — a marker of rapid neuronal destruction, supportive though not entirely specific.
- Real-Time Quaking-Induced Conversion (RT-QuIC) assay — a highly sensitive and specific CSF-based test, now considered a key diagnostic tool, detecting the seeding/conversion activity of abnormal prion protein.
- Definitive diagnosis requires brain biopsy/autopsy, demonstrating spongiform change and detection of protease-resistant PrP^Sc by immunohistochemistry/Western blot — carrying significant biosafety implications given the agent’s resistance to standard sterilization (requiring special decontamination protocols — e.g., prolonged autoclaving with sodium hydroxide pretreatment, or incineration of disposable instruments).
No treatment is currently available; management is purely supportive, and prevention centres on strict infection-control precautions for surgical instruments used in suspected/confirmed cases and screening of at-risk tissue/blood donations.